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The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer.

Malander, Susanne LU orcid ; Rambech, Eva LU ; Kristoffersson, Ulf LU ; Halvarsson, Britta LU ; Ridderheim, Mona LU ; Borg, Åke LU and Nilbert, Mef LU (2006) In Gynecologic Oncology 101(2). p.238-243
Abstract
Objective. Ovarian cancer has one of the highest fractions of hereditary cases. The hereditary breast and ovarian cancer syndrome, primarily due to mutations in BRCA1 and BRCA2, is the main cause of heredity, but also the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome confers an increased risk of ovarian cancer. In order to clarify the contribution of HNPCC to the development of ovarian cancer, we collected data on family history of cancer and characterized MMR function in a consecutive series of 128 tumors unselected for age at diagnosis and previously characterized for BRCA gene mutations. Methods. Expression of the MMR proteins MLH1 PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry using tissue microarray sections.... (More)
Objective. Ovarian cancer has one of the highest fractions of hereditary cases. The hereditary breast and ovarian cancer syndrome, primarily due to mutations in BRCA1 and BRCA2, is the main cause of heredity, but also the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome confers an increased risk of ovarian cancer. In order to clarify the contribution of HNPCC to the development of ovarian cancer, we collected data on family history of cancer and characterized MMR function in a consecutive series of 128 tumors unselected for age at diagnosis and previously characterized for BRCA gene mutations. Methods. Expression of the MMR proteins MLH1 PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry using tissue microarray sections. Tumors with reduced staining or loss of staining were also analyzed for microsatellite instability (MSI). Results. Loss of MMR protein expression was identified in 3 ovarian cancers, all of which had a MSI-high phenotype. DNA sequence analysis revealed disease-causing germline mutations (deletions of exons 4-6 in MLHI and a 1-nucleotide deletion in exon 5 of MSH6) in two patients diagnosed at ages 40 and 49 years, both of whom had family histories suggestive of HNPCC. The genetic defect in the third case, which was a 47-year old woman without knowledge about her family history with loss of MLH1/PMS2 expression in the tumor tissue, remains elusive. A family history suggestive of HNPCC was identified in an additional case, but this tumor showed normal, retained MMR protein expression and a microsatellite stable phenotype. Conclusions. About 2% of ovarian cancer is caused by germline mutations in the MMR-genes, a minor proportion as compared to the contribution of the BRCA-genes (11% in the present series). However, identification of HNPCC patients is important since it allows inclusion of high-risk individuals into control programs aimed at preventing the more frequent colorectal and endometrial cancers. Tumors within the HNPCC-spectrum should therefore be included when recording a family history of cancer among patients diagnosed with ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ovarian cancer, heredity, HNPCC, MMR
in
Gynecologic Oncology
volume
101
issue
2
pages
238 - 243
publisher
Academic Press
external identifiers
  • pmid:16360201
  • wos:000237813700011
  • scopus:33646408125
ISSN
1095-6859
DOI
10.1016/j.ygyno.2005.10.029
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Clinical Genetics (013022003), Oncology, MV (013035000), Pathology, (Lund) (013030000)
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83f9ad4d-1ac8-4ae9-88ab-486297139d7e (old id 148621)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16360201&dopt=Abstract
date added to LUP
2016-04-01 11:50:01
date last changed
2022-01-26 18:57:53
@article{83f9ad4d-1ac8-4ae9-88ab-486297139d7e,
  abstract     = {{Objective. Ovarian cancer has one of the highest fractions of hereditary cases. The hereditary breast and ovarian cancer syndrome, primarily due to mutations in BRCA1 and BRCA2, is the main cause of heredity, but also the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome confers an increased risk of ovarian cancer. In order to clarify the contribution of HNPCC to the development of ovarian cancer, we collected data on family history of cancer and characterized MMR function in a consecutive series of 128 tumors unselected for age at diagnosis and previously characterized for BRCA gene mutations. Methods. Expression of the MMR proteins MLH1 PMS2, MSH2, and MSH6 was analyzed by immunohistochemistry using tissue microarray sections. Tumors with reduced staining or loss of staining were also analyzed for microsatellite instability (MSI). Results. Loss of MMR protein expression was identified in 3 ovarian cancers, all of which had a MSI-high phenotype. DNA sequence analysis revealed disease-causing germline mutations (deletions of exons 4-6 in MLHI and a 1-nucleotide deletion in exon 5 of MSH6) in two patients diagnosed at ages 40 and 49 years, both of whom had family histories suggestive of HNPCC. The genetic defect in the third case, which was a 47-year old woman without knowledge about her family history with loss of MLH1/PMS2 expression in the tumor tissue, remains elusive. A family history suggestive of HNPCC was identified in an additional case, but this tumor showed normal, retained MMR protein expression and a microsatellite stable phenotype. Conclusions. About 2% of ovarian cancer is caused by germline mutations in the MMR-genes, a minor proportion as compared to the contribution of the BRCA-genes (11% in the present series). However, identification of HNPCC patients is important since it allows inclusion of high-risk individuals into control programs aimed at preventing the more frequent colorectal and endometrial cancers. Tumors within the HNPCC-spectrum should therefore be included when recording a family history of cancer among patients diagnosed with ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved.}},
  author       = {{Malander, Susanne and Rambech, Eva and Kristoffersson, Ulf and Halvarsson, Britta and Ridderheim, Mona and Borg, Åke and Nilbert, Mef}},
  issn         = {{1095-6859}},
  keywords     = {{ovarian cancer; heredity; HNPCC; MMR}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{238--243}},
  publisher    = {{Academic Press}},
  series       = {{Gynecologic Oncology}},
  title        = {{The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer.}},
  url          = {{http://dx.doi.org/10.1016/j.ygyno.2005.10.029}},
  doi          = {{10.1016/j.ygyno.2005.10.029}},
  volume       = {{101}},
  year         = {{2006}},
}